In vitro research on the identification of increased risk for pancreatic cancer within families with pancreatic cancer with and without other solid tumors was based on the hypothesis that a cell considered normal by all criteria in a clinically normal individual when grown in culture would demonstrate such a mutant cancer-prone genotype. This hypothesis was based on in vitro research on the inborn errors of metabolism and the heritable colon cancer syndromes. Dermal (fibroblast and epithelial) cultures were established from affected members, family members considered to be at increased risk and family members by marriage who did not have a family history of solid tumors as controls. Increased in vitro tetraploidy has been observed in members at increased risk for pancreatic cancer in association with other solid tumors (offspring of affecteds). On the basis of this finding, increased in vitro tetraploidy may be useful in detecting risk for pancreatic cancer in families with heritable cancer syndromes involving more than 1 organ site. A cancer-prone gene expressed as solid tumors including pancrease in vivo may be detected in vitro by increased tetraploidy. Further research should demonstrate if increased in vitro tetraploidy identifies members at increased risk in families with pancreatic cancer.